PROJECT SUMMARY/ABSTRACT Lung cancer is a disease of older adults with a median age at diagnosis of 70. Older adults with lung cancer are at increased risk for treatment toxicity, which can result in functional impairment and decreased quality of life (QOL). These outcomes are critically important to patients, yet fundamental gaps exist in our knowledge of how lung cancer treatment impacts functional status and QOL in older adults. The traditional framework for cancer treatment toxicity focuses on adverse events graded according to the Common Terminology Criteria (CTC) for adverse events, which do not capture functional status or QOL. While CTC-graded adverse events provide only a narrow definition of cancer treatment toxicity, they remain the primary source of data used by oncologists to describe potential side effects to patients. Furthermore, recent advances in drug development for metastatic lung cancer have introduced novel immunotherapy and second- and third-generation targeted therapies. However, no data are available on how these new systemic treatments impact functional status and QOL over time in older adults with lung cancer. We propose an expanded geriatric definition of cancer treatment toxicity that encompasses how treatment impacts patients? lives on a daily basis with functional status and QOL as the cornerstones of assessment. We will conduct a cohort study of 75 metastatic lung cancer patients age >65 starting systemic treatment with chemotherapy, immunotherapy, and/or targeted therapy. Patients will undergo geriatric assessment to measure functional status (i.e., activities of daily living (ADLs), instrumental ADLs, physical performance) and QOL (i.e., global QOL, patient-reported symptoms) prior to treatment initiation and at 1, 2, 4, and 6 months. We aim to longitudinally characterize patient-centered measures of treatment toxicity (i.e., functional status, QOL) in older adults with metastatic lung cancer during systemic treatment and to determine the associations of CTC-graded adverse events over time with trajectories of functional status and QOL. In addition, we will determine associations of demographic, clinical, and geriatric assessment characteristics with trajectories of functional status and QOL. A subgroup of 20 to 30 patients will participate in 2 semi-structured interviews prior to treatment initiation and at 2 months to explore how treatment impacts their lives globally and to identify facilitators and barriers to maintaining functional status and QOL during treatment. Primary mentorship will be provided by Louise Walter, MD (Geriatrics) and Christine Miaskowski, RN, PhD (Cancer Symptom Research). Additional mentors include Arti Hurria, MD (Geriatric Oncology), Alex Smith, MD, MS, MPH (Qualitative Research), and Bruce Cooper, PhD (Statistics). This study will provide valuable real-world data on patient-centered functional status and QOL outcomes to inform treatment discussions and decisions for older adults with metastatic lung cancer. These data will serve as the foundation for future studies to develop and validate risk prediction models for decrements in functional status and QOL and interventions to improve these outcomes in older adults during lung cancer treatment.